Ophthalmic tear film disorders or dry eye can be caused by traumatic orbital injury to the neural innervation or circulation to the lacrimal or tear gland, lacrimal gland neoplasia, congenital lacrimal gland disease, endocrine disease, and immune mediated eye and systemic diseases that affect the lacrimal gland. Lymphocytic invasion of the lacrimal gland results in quantitative and qualitative tear film disease. Immune mediated dry eye conditions include but are not limited to keratoconjunctivitis sicca (KCS) and Sjögren's syndrome (SS). Persistent corneal erosions and conjunctivitis can accompany KCS. Clinical signs of KCS include ocular discomfort, blurred vision, mucoid ocular discharge, conjunctival hyperemia, tear film instability, blepharospasm, recurrent corneal erosion and ulceration, corneal vascularization and pigmentation, and can ultimately lead to blindness if treatment is ineffective.
Treatments for dry eye and other related immune mediated diseases of the eye include anti-inflammatory drugs, antibiotics, antiproteases, artificial tears, and immunomodulatory drugs. Therapy may not be effective due to ocular irritation caused specifically by the fact the topical drug used is inherently irritating or the drug formulation is irritating. Poor ocular corneal contact time can result in poor drug bioavailability, and systemic absorption of the topical drug can also cause, low tear film and corneal drug levels. Failure of the drug to return tear production to normal levels may occur if the specific drug is not sufficiently able to prevent the immune mediated attack on the lacrimal gland. Poor drug stability, incorrect drug pH, variation in reproducibility of batch-to-batch dry eye drug production, difficulties in drug sterilization during drug production, low drug loading in sustained release techniques, and/or limitations for large-scale drug production are also problems in pharmacologic production of drugs for the treatment of dry eye and other related immune mediated diseases of the eye.
There is thus a continued need for improved immunosuppressive treatments, formulations and methods for the treatment of dry eye and/or other related immune mediated diseases of the eye.